Ablative Radiosurgery Research Articles

Proton Based Stereotactic Radiotherapy for Skull Base Patients: Dosimetric Comparison to 4 Modern Radiation Treatment Modalities

Re-irradiation with ablative doses to a smaller target volume and strict critical structure constraint is a challenge for modern radiation planning and delivery systems. Several advanced radiation treatment techniques can be used for fractionated stereotactic ablative radiosurgery (FSRS) in select patients with unresectable recurrent head and neck tumors. In this study, in order to better understand the dosimetry advantage of each technique, we compare the stereotactic treatment plans of our new small spot size Hitachi proton treatment unit to those of CyberKnife stereotactic radiosurgery (CK), Gamma Knife radiosurgery (GK), volumetric modulated arc therapy (VMAT), and MR Linac radiotherapy (MRL). Ten FSRS skull base patients treated at our institution using VMAT (n = 5) or GK (n = 5) techniques. Intensity-modulated proton therapy (IMPT) plans were created in Raystation using Monte Carlo dose calculation algorithm. VMAT, CK, GK and MRL plans were generated in RayStation, Accuray Precision, Leksell Gamma Plan, and Monaco treatment planning systems, separately. Planning goals were to achieve the best target coverage of prescribed dose without compromising the critical organs at risk dose volume constraints of the clinical treatment plans. Plans were compared based on percent CTV coverage, Paddick conformity index (PCI), gradient index (GI, V50/V100), dose homogeneity index (HI, (D2-D98)/D50), low dose bath volume (LDBV, ratio of total volume irradiated between 20% and 50% prescription dose and the target volume), beam-on-time (BOT), and mean/maximum doses to brainstems. The median target volume was 15.5 cm3 (range 1.0 - 36.23 cm3). The prescription was 45 Gy in 5 fractions for VMAT patients, and 21 - 27 Gy in 3 fractions for GK patients. The comparison of the treatment plans of these 5 delivery modalities was shown in table. All techniques achieved comparable CTV coverage. GI was superior for GK plans and outstanding in CK and IMPT plans. IMPT plans were also outstanding in regard to BOT and PCI. Significantly improved HI, LDBV and brainstem mean doses were achieved in IMPT plans. For adjacent brainstem and other OARs, maximum doses were comparable among all techniques. In these five advanced radiation therapy modalities, proton therapy SBRT showed dosimetric advantage over other modalities to spare nearby OARs without sacrifice of target coverage. Further studies are needed to utilize this clinical benefit and investigate plan robustness.

449 Carbon Fibre Versus Titanium Implant Construct in Separation Surgery with Post Adjuvant Stereotactic Ablative Radiotherapy for Spinal Oligometastatic Disease

Abstract Aim Radical treatment for Spinal Oligometastatic Disease (OMD) was often traditionally treated with morbid Tomita En Bloc Spondylectomy. Now, Stereotactic Ablative Radiosurgery (SABR) provides curative tumour ablation without open surgery, reduced cord toxicity and better pain management. SABR delivered postoperatively to Separation Surgery (SS) has shown excellent mortality rates, infection control, maximum local-control, and better pain management. This study is the first to compare clinical safety of carbon-fibre implantation (CFI) comparing to titanium implantation (TI). Method Retrospective review of OMD/OPD cases that underwent separation surgery with postoperative SABR investigating tumour histology, OMD type, instrumentation used for SS (CFI versus TI), mortality, local recurrence (LR), pain management, infection, complications, hospital length of stay, ICU length of stay and palliative outcomes at a quaternary level-1 spinal unit. Results 79 patients were in the OMD pathway, 36 patients underwent SS with/without SABR. 20 patients had SS with TI. 16 patients had SS with CFI. SS with TI±SABR: 30-day mortality-10%, 12-month mortality-15%. SS with TI+SABR: 30-day mortality-0% 12-month mortality-0%, 12-month LR-0% TI: Infection-4% SS with CFI±SABR: 30-day mortality-6%, 3-year mortality-12.5%. SS with CFI+SABR: 30-day mortality-0% 12-month mortality-0%, 12-month LR-0% CFI: Infection-0% Pain in both groups were associated with PD cases only. Conclusions SS with postoperative SABR regardless of construct material demonstrated excellent outcomes. CFI demonstrated to be superior to TI. When postoperative SABR was absent from treatment, patients had complications and was demoted to palliative decompression with neurological symptom management. This highlights the importance of SABR in conjunction to SS.

PD-0655 Stereotactic ablative radiosurgery (SABR) for spinal metastases: 12-years of experience

PD-0655 Stereotactic ablative radiosurgery (SABR) for spinal metastases: 12-years of experience

Curative treatment of pancreatic functioning insulinoma with stereotactic ablative radiation therapy: case report

Insulinoma is the most common pancreatic neuroendocrine tumor (NET). It is a rare disease account for 1-2% of pancreatic tumors and affect approximately up to 3 patients per million per year. complete surgical resection or debulking are standard of care option. However, surgery is associated with short and long-term post-operative morbidity and may not be appropriate for all patients. In This case we present management and cure of a case of functioning insulinoma with stereotactic ablative radiosurgery in an unfit patient for surgery.

Stereotactic Proton Ablative Radiosurgery of the Spine

To report the techniques of treating primary tumors and metastases of the spine with stereotactic proton ablative radiotherapy.Robustly optimized IMPT plans were generated using either the Single-field optimization (SFO) or the multi-field optimization (MFO) method in the treatment planning system. Patients with primary and metastatic lesions of the spine, who underwent curative-intent, received ablative pencil-beam scanning proton therapy between July 2015 and October 2019. Patients were immobilized with thermoplastic mask or vac lok, indexed knee cushion, and memory foam. Radiotherapy was delivered CT-on-Rail image guidance. MRI, CT, and/or PET-CT were assessed for radiographic local control. Outcomes were measured from radiation end date to last imaging. Acute and long-term adverse events (AE) were assessed based on CTCAE v4.0.Forty-four patients were identified. Forty-nine unique metastatic spine sites were treated, C-spine (n = 2), T-spine (13), L-spine (18), and sacrum (16). The median age was 64. 44% were prostate histology. 80% had prior overlapping radiotherapy fields, and 20% were retreatment. The median dose per fraction and number of fractions were 13 Gy (R, 10-22 Gy) and 3 (R, 1-5). The Median follow-up was 22.2 months. Overall survival at 1 and 2 years was 79.1% and 73.8%. Forty-five patients were surveilled with imaging. The radiographic local control at 1 and 2 years was 74.0% and 56.2%. Local failure-free survival at 1 and 2 years was 60.6% and 40.9%. All patients were assessed during and following radiotherapy for acute and long-term toxicities. Acutely, 9 (18%) patients experienced a pain flare with 4, requiring initiation or increased opioids or steroids for pain management. Three patients experienced acute grade 1 peripheral sensory neuropathy, and one patient, acute grade 1 esophagitis. Long term, there was one de novo vertebral body compression fracture requiring vertebroplasty and three patients with grade 1-2 sensory peripheral neuropathy.Stereotactic proton ablative radiotherapy for the treatment of tumors and metastases of the spine is a safe and effective treatment modality.M. Dougherty: None. T.C. Mullikin: None. S.S. Park: None.

Radiation treatment planning study to investigate feasibility of delivering Immunotherapy in Combination with Ablative Radiosurgery to Ultra-High DoSes (ICARUS).

PurposeImmune checkpoint inhibitors improve survival in metastatic diseases for some cancers. Multisite SBRT with pembrolizumab (SBRT + Pembro) was shown to be safe with promising local control using biologically effective doses (BEDs) = 95–120 Gy. Increased BED may improve response rate; however, SBRT doses are limited by surrounding organs at risk (OARs). The purpose of this work was to develop and validate methods for safe delivery of ultra‐high doses of radiation (BED10 > 300) to be used in future clinical trials.Methods and MaterialsThe radiation plans from 15 patients enrolled on a phase I trial of SBRT + pembro were reanalyzed. Metastatic disease sites included liver (8/15), inguinal region (1/15), pelvis (2/15), lung (1/15), abdomen (1/15), spleen (1/15), and groin (1/15). Gross tumor volumes (GTVs) ranged from 80 to 708 cc. Following the same methodology used in the Phase I trial on which these patients were treated, GTVs > 65 cc were contracted to a 65 cc subvolume (SubGTV) resulting in only a portion of the GTV receiving prescription dose. Volumetric modulated arc therapy (VMAT) was used to plan treatments BED10 = 360 Gy. Plans utilizing both 6FFF and 10FFF beams were compared to clinical plans delivering BED10 = 112.50 Gy. The target primary goal was V100% > 95% with a secondary goal of V70% > 99% and OAR objectives per the trial. To demonstrate feasibility, plans were delivered to a diode array phantom and evaluated for fidelity using gamma analysis.ResultsAll 30 plans met the secondary coverage goal and satisfied all OAR constraints. The primary goal was achieved in 12/15 of the 6FFF plans and 13/15 of the 10FFF plans. Average gamma analysis passing rate using criteria of 3% dose difference and 3, 2, and 1 mm were 99.1 ± 1.0%, 98.5 ± 1.6%, and 95.1 ± 3.8%, respectively.ConclusionNovel VMAT planning approaches with clinical treatment planning software and linear accelerators prove capable of delivering radiation doses in excess of 360 Gy BED10 to tumor subvolumes, while maintaining safe OAR doses.

English

English

Feasibility of Delivering Immunotherapy with Concomittant Ablative Radiosurgery to Ultra-high DoSes (ICARUS)

Immune checkpoint inhibitors, such as pembrolizumab (pembro), have been shown to be efficacious in improving survival. However, there is only an overall response rate of 5% after 3rd/4th line therapy with pembro alone. Our initial trial combining SBRT with pembro (NRG BR001) was shown to be safe (<9% grade 3 toxicity) with promising local control and overall survival using a biologically effective dose (BED) of roughly 100 Gy. One strategy to increase the response rate is to increase the BED. However, SBRT doses are limited by dosimetric constraints of surrounding organs at risk (OARs). The purpose of this work was to determine if ultra-high radiation (BED >200) could be delivered while still respecting OAR tolerances for patients receiving SBRT + pembro. Five patients enrolled on an institutional phase I trial investigating the safety of SBRT + pembro were analyzed. Disease sites included liver (3/5), inguinal region (1/5) and pelvis (1/5). The trial dictated that gross tumor volumes (GTVs) >65 cc were contracted to a 65cc subvolume for planning target volume (PTV) definition (3 mm margin). Volumetric modulated arc therapy (VMAT) was used to plan treatments prescribing 90Gy in 3 fractions (BED10 = 360 Gy). Plans utilizing both 6FFF and 10FFF beams were created and compared to the clinical plans delivering 45 Gy in 3 fractions (BED10 = 112.50 Gy). The target coverage primary goal was V100% > 95% with a secondary goal of V70% > 99%. OAR tolerances were prioritized. OAR objectives followed the trial protocol. To demonstrate deliverability, plans were delivered to a quality assurance phantom containing a diode array and evaluated for fidelity using gamma analysis. Using 6FFF, all liver tumors and the pelvic mass met the primary coverage goal and the inguinal mass met the secondary coverage goal. Using 10 FFF, the inguinal, pelvis and one liver mass met the primary coverage goal and the remaining two liver masses met the secondary coverage goal. Most importantly, for all plans, OAR dose constraints were met. GTV D100% ranged from BEDs of 167-504 Gy using 6FFF and 106-470 Gy using 10FFF. Target coverage was generally degraded in the 10FFF vs. 6FFF plans; however, the 10FFF allowed for improved skin sparing and provides a logistical advantage of 2x faster dose rate. Gamma analysis of delivered plans using 3%/1mm criteria passed with average rate of 98.14%. This study suggests that VMAT approaches are capable of delivering radiation doses in excess of 300 Gy BED10 to tumors at various body sites, while maintaining safe OAR doses. These plans have been shown to be deliverable using standard QA approaches and will be incorporated into an upcoming clinical trial. In the era of precision image guided radiation therapy, these results argue that we may have the capability to vastly increase SBRT doses safely and improve the efficacy of concomitant SBRT and immunotherapy.

Stereotactic Ablative Radiosurgery (SABR) of Dorsal Sacral Lateral Nerve Branches for Treatment of Sacroiliac Pain – a Dosimetric Feasibility Study Exploring the Role of Noninvasive SABR in Place of Bipolar Radiofrequency Ablation

Sacroiliac (SI) joint dysfunction can be the underlying cause of low back pain in up to 15 to 25% cases. Bipolar RFA lesioning of the lateral branches of the S1 to S3 dorsal rami, which innervate the SI joint, can provide clinical relief of pain in patients. Due to the irregular paths of the nerves travelling to the SI joint and the many small nerve branches, it can be technically difficult to ablate the entire area at risk with RFA, which may make relief less effective. Ablative therapies such as SABR can be used for nerve ablation in settings such as trigeminal neuralgia. We hypothesize that LINAC-based SABR may be a noninvasive option for delivering ablative radiation dose to the branching dorsal lateral nerves while maintaining low doses to the surrounding organs at risk (OARs). The ultimate goal being equivalent or improved pain relief when compared to RFA. CT images of the lumbosacral spine in 1.25mm slices were obtained from 5 anonymized patients with standard immobilization who were treated at our facility for issues unrelated to back pain. An interventional radiologist who regularly performs injections and RFA contoured the dorsal nerves of the SI joint for the targeted strips of the dorsal sacral surface bilaterally. PTV volumes included a 1mm expansion. Four VMAT beams targeting the PTV were used to optimize the dose distribution and spare the OARs. The following table shows the relevant treatment volumes, PTV coverage, and OAR doses. We avoided excessive doses to the surrounding OAR structures in the plans for all 5 patients bilaterally. A thin 1mm strip of bone was included in the PTV. Excessive bone doses and volumes were minimized in an attempt to lower risks for osteoradionecrosis. Coverage was acceptable with an average of 49Gy covering the 95% IDL. This study demonstrates the feasibility of delivering ablative doses to the lateral branches of the dorsal sacral nerves that innervate the SI joint. Due to its posterior location all OARs received acceptable doses, other than the portion of bone immediately deep to the treated strip of tissue. By minimizing the treated bone volume while covering the pathways of the traveling nerves, we hope to minimize risk of osteoradionecrosis. This unique approach requires further study but has the potential to replace invasive interventions and allow for decrease in opiate requirement and consumption.Abstract 3601; Table 1Structure and parameterMean ± SDPTV volume (cm3)4.45±1.20Spinal canal Dmax (cGy)218±172Bladder mean (cGy)34±17Bowel mean (cGy)147±60Bone mean (cGy)535±147Bone volume over 30 Gy (cc)21±15 Open table in a new tab

Promising Clinical Outcome With Long Term Follow-Up After Body Gamma Knife Stereotactic Radiosurgery for Patients With Early Stage Non-small Cell Lung Cancer.

Introduction: Stereotactic ablative radiosurgery (SRS) or stereotactic ablative body radiotherapy (SABR) is the standard treatment for patients with inoperable early stage non-small cell lung cancer (NSCLC), the body gamma knife SRS (ɤ-SRS) is a special SABR technology developed in China. This study prospectively assessed the clinical outcome, toxicity and cost following body ɤ-SRS for early stage NSCLC.Methods: From 2007 to 2010, a total of 29 patients with early stage NSCLC were prospectively enrolled in this study. The prescription dose for Planning Target Volume (PTV), Clinical Target Volume (CTV), and Gross Target Volume (GTV) were 50, 60, and 70 gray (Gy) in 10 fractions. Isodose curves of 50, 60, and 70% covered at least 100% of PTV, 90% of CTV, and 80% of GTV, respectively. The body ɤ-SRS was delivered 5 days per week and completed in 2 weeks.Results: Median follow-up time was 62.0 (range 11.1-140.3) months. 1-, 3-, 5-year OS rates were 93.1%, 72.0%, 60.3%; PFS rates were 86.2, 64.2 and 48.8%; and LR, RR, and DM rates were 10.9%, 21.4%, 29.0%. The median cost of the body ɤ-SRS during treatment was 4,838 (range 4,615–4,923) dollars and the median cost through 5 years was 36,960 (range 9920-56,824) dollars.Conclusion: With existing clinical data, the body ɤ-SRS is an effective treatment option for patients with medically inoperable early stage NSCLC or patients who do not prefer operation, as they may benefit from the minimized toxicity. Due to excellent cost effectiveness, the availability of the body ɤ-SRS will expand, especially in developing nations, and underdeveloped countries.

Commentary: Phase I Trial of Carboplatin and Gemcitabine Chemotherapy and Stereotactic Ablative Radiosurgery for the Palliative Treatment of Persistent or Recurrent Gynecologic Cancer.

Background: We conducted a phase I trial to determine the safety of systemic chemotherapy prior to abdominopelvic robotic stereotactic ablative radiotherapy (SABR) in women with persistent or recurrent gynecologic cancers. Methods: Patients were assigned to dose-finding cohorts of day-1 carboplatin (AUC 2 or 4) and gemcitabine (600 or 800 mg/m2) followed by day-2 to day-4 Cyberknife SABR (8Gy X 3 consecutive daily doses). Toxicities were graded prospectively by common terminology criteria for adverse events, version 4.0. SABR target and best overall treatment responses were recorded according to response evaluation criteria in solid tumors, version 1.1. Findings: The maximum tolerated dose of chemotherapy preceding SABR was carboplatin AUC 4 and gemcitabine 600 mg/m2. One patient experienced manageable, dose-limiting grade 4 neutropenia, grade 4 hypokalemia, and grade 3 nausea attributed to study treatment. One patient had a late grade 3 rectovaginal fistula 16 months after trial therapy. Among 28 SABR targets, 22 (79%) showed a partial response and six (21%) remained stable. Interpretation: Systemic chemotherapy may be given safely prior to abdominopelvic robotic SABR with further investigation warranted. Funding: National Institutes of Health grant P30 CA43703

A new era of thoracic oncology? Ex-vivo stereotactic ablative radiosurgery within Ex-vivo Lung Treatment System as a hybrid therapy for unresectable locally advanced pulmonary malignancies

The concept of oligometastases is the medical rationale for a local treatment of a limited number of metastatic tumor manifestations. Patients with pulmonary oligometastases are candidates for surgery or radiotherapy, however there are a number of technical issues that limit treatment. Technical issues relating to radiotherapy include organs at risk of irradiation, chest wall toxicity and decreased precision of tumor targeting because of breathing movements. Technical issues relating to surgery include loss of lung parenchyma and unresectability. We propose the hypothesis that ex-vivo radiosurgery as new hybrid technique in thoracic oncology has the capability to overcome these technical issues and will expand the medical spectrum in thoracic oncology. The proposed – highly complex – technique consists of surgical lung explantation, followed by stereotactic radiotherapy during ex-vivo perfusion followed by surgical re-implantation.

Definitive Radiation Therapy for Early-Stage Breast Cancer: Dosimetric Feasibility of Stereotactic Ablative Radiosurgery (SABR) for Intact Breast Tumors

Definitive Radiation Therapy for Early-Stage Breast Cancer: Dosimetric Feasibility of Stereotactic Ablative Radiosurgery (SABR) for Intact Breast Tumors

Phase I Trial of Carboplatin and Gemcitabine Chemotherapy and Stereotactic Ablative Radiosurgery for the Palliative Treatment of Persistent or Recurrent Gynecologic Cancer.

We conducted a phase I trial to determine the safety of systemic chemotherapy prior to abdominopelvic robotic stereotactic ablative radiotherapy (SABR) in women with persistent or recurrent gynecologic cancers. Patients were assigned to dose-finding cohorts of day 1 carboplatin (AUC 2 or 4) and gemcitabine (600 or 800 mg/m(2)) followed by day 2 to day 4 Cyberknife SABR (8 Gy × three consecutive daily doses). Toxicities were graded prospectively by common terminology criteria for adverse events, version 4.0. SABR target and best overall treatment responses were recorded according to response evaluation criteria in solid tumors, version 1.1. The maximum tolerated dose of chemotherapy preceding SABR was carboplatin AUC 4 and gemcitabine 600 mg/m(2). One patient experienced manageable, dose-limiting grade 4 neutropenia, grade 4 hypokalemia, and grade 3 nausea attributed to study treatment. One patient had a late grade 3 rectovaginal fistula 16 months after trial therapy. Among 28 SABR targets, 22 (79%) showed a partial response and 6 (21%) remained stable. Systemic chemotherapy may be given safely prior to abdominopelvic robotic SABR with further investigation warranted.

TU-AB-201-06: Evaluation of Electromagnetically Guided High- Dose Rate Brachytherapy for Ablative Treatment of Lung Metastases

Purpose: The advent of electromagnetic navigation bronchoscopy has enabled minimally invasive access to peripheral lung tumors previously inaccessible by optical bronchoscopes. As an adjunct to Stereotactic Ablative Radiosurgery (SABR), implantation of HDR catheters can provide focal treatments for multiple metastases and sites of retreatments. The authors evaluate a procedure to deliver ablative doses via Electromagnetically-Guided HDR (EMG-HDR) to lung metastases, quantify the resulting dosimetry, and assess its role in the comprehensive treatment of lung cancer. Methods: A retrospective study was conducted on ten patients, who, from 2009 to 2011, received a hypo-fractionated SABR regimen with 6MV VMAT to lesions in various lobes ranging from 1.5 to 20 cc in volume. A CT visible pathway was delineated for EM guided placement of an HDR applicator (catheter) and dwell times were optimized to ensure at least 98% prescription dose coverage of the GTV. Normal tissue doses were calculated using inhomogeneity corrections via a grid-based Boltzmann solver (Acuros_BV_1.5.0). Results: With EMG-HDR, an average of 83% (+/−9% standard deviation) of each patient's GTV received over 200% of the prescription dose, as compared to SABR where the patients received an average maximum dose of 125% (+/−5%). EMG-HDR enabled a 59% (+/−12%) decrease in the aorta maximum dose, a 63% (+/−26%) decrease in the spinal cord max dose, and 57% (+/−23%) and 70% (+/−17%) decreases in the volume of the body receiving over 50% and 25% of the prescription dose, respectively. Conclusion: EMG-HDR enables delivery of higher ablative doses to the GTV, while concurrently reducing surrounding normal tissue doses. The single catheter approach shown here is limited to targets smaller than 20 cc. As such, the technique enables ablation of small lesions and a potentially safe and effective retreatment option in situations where external beam utility is limited by normal tissue constraints.

Stereotactic ablative radiosurgery for locally advanced or recurrent skull base malignancies with prior external beam radiation therapy.

Purpose: Stereotactic ablative radiotherapy (SABR) is an attractive modality to treat malignancies invading the skull base as it can deliver a highly conformal dose with minimal toxicity. However, variation exists in the prescribed dose and fractionation. The purpose of our study is to examine the local control, survival, and toxicities in SABR for the treatment of previously irradiated malignant skull base tumors.Materials and methods: A total of 31 patients and 40 locally advanced or recurrent head and neck malignancies involving the skull base treated with a common SABR regimen, which delivers a radiation dose of 44 Gy in 5 fractions from January 1st, 2004 to December 31st, 2013, were retrospectively reviewed. The local control rate (LC), progression-free survival rate, overall survival (OS) rate, and toxicities were reported.Results: The median follow-up time of all patients was 11.4 months (range: 0.6–67.2 months). The median tumor volume was 27 cm3 (range: 2.4–205 cm3). All patients received prior external beam radiation therapy with a median radiation dose of 64 Gy (range: 24–75.6 Gy) delivered in 12–42 fractions. Twenty patients had surgeries prior to SABR. Nineteen patients received chemotherapy. Specifically, eight patients received concurrent cetuximab (Erbitux™) with SABR. The median time-to-progression (TTP) was 3.3 months (range: 0–16.9 months). For the 29 patients (93.5%) who died, the median time from the end of first SABR to death was 10.3 months (range: 0.5–41.4 months). The estimated 1-year OS rate was 35%. The estimated 2-year OS rate was 12%. Treatment was well-tolerated without grade 4 or 5 treatment-related toxicities.Conclusion: Stereotactic ablative radiotherapy has been shown to achieve low toxicities in locally advanced or recurrent, previously irradiated head and neck malignancies invading the skull base.